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Pancreatic Cancer pp 403–418Cite as

Hedgehog Signaling Pathways in Pancreatic Cancer Pathogenesis

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Abstract:

Recent research has identified the Hedgehog signaling pathway as a key player in pancreatic cancer. The pathway is normally silent in the adult pancreas, but it gets activated in precursor lesions of pancreatic cancer as well as in invasive and metastatic pancreatic adenocarcinoma. Interestingly, mutations in the components of Hedgehog signaling have not been identified in pancreatic cancer; instead, the mechanism of activation relies on overexpression of one of the pathway ligands, Sonic Hedgehog, by the tumor cells. It is under investigation whether the secreted Hedgehog ligand mediates interactions among different cell types within the tumor. Our current knowledge indicates that the Hedgehog signaling pathway gets activated downstream of Kras (which is activated through a mutation in the vast majority of pancreatic cancers) and it synergizes with the Kras activity to promote tumor progression. Interestingly, the activity of the Hedgehog pathway appears to regulate processes such as tumor metastasis, one of the factors that preclude treatment in human patients. Current research is aimed at fully understanding the role of the pathway in pancreas cancer formation and progression and at establishing whether inhibition of this pathway might represent a valid approach to treat pancreatic cancer in the clinic.

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Authors and Affiliations

  1. University of Michigan, Ann Arbor, MI, USA

    Marina Pasca di Magliano

  2. University of California, San Francisco, CA, USA

    Matthias Hebrok

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  1. Marina Pasca di Magliano
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  2. Matthias Hebrok
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Pasca di Magliano, M., Hebrok, M. (2010). Hedgehog Signaling Pathways in Pancreatic Cancer Pathogenesis. In: Pancreatic Cancer. Springer, New York, NY. https://doi.org/10.1007/978-0-387-77498-5_16

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